1. Field of the Invention
The present invention relates to novel dialkylphenyl compounds having β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. This invention also relates to pharmaceutical compositions comprising such compounds, processes and intermediates for preparing such compounds and methods of using such compounds, for example, to treat pulmonary disorders.
2. State of the Art
Pulmonary disorders, such as asthma and chronic obstructive pulmonary disease (COPD), are commonly treated with bronchodilators. One type of bronchodilator used to treat pulmonary disorders consists of β2 adrenergic receptor (adrenoceptor) agonists, such as albuterol, formoterol and salmeterol. These compounds are generally administered by inhalation. Another type of bronchodilator consists of muscarinic receptor antagonists (anticholinergic compounds), such as ipratropium and tiotropium. These compounds are also typically administered by inhalation.
Pharmaceutical compositions containing a combination of a β2 adrenergic receptor agonist and a muscarinic receptor antagonist are known in the art for use in treating pulmonary disorders. For example, U.S. Pat. No. 6,433,027, issued Aug. 13, 2002, discloses medicament compositions containing a muscarinic receptor antagonist, such as tiotropium bromide, and a β2 adrenergic receptor agonist, such as formoterol fumarate.
Additionally, compounds having both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity are known in the art. For example, U.S. Pat. No. 7,141,671, issued Nov. 28, 2006, discloses biphenyl compounds having both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Compounds possessing both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity are highly desirable since such compounds provide bronchodilation through two independent modes of action while having single molecule pharmacokinetics.
When treating pulmonary disorders, it is particularly useful to provide therapeutic agents that have a long duration of action, i.e., a duration of at least about 24 hours, when administered by inhalation so that patients only need to administer the therapeutic agent once a day or less. Not all dual-acting compounds disclosed previously in the art possess this desirable property.
Accordingly, a need exists for novel compounds having both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity that possess a long duration of action when administered to a patient by inhalation.